Restless Legs Syndrome (RLS) is best described as irresistible leg movements often accompanied by a creeping sensation deep in the limbs. Its is reported to be the fourth leading cause of insomnia after psychiatric disorders, drug abuse, and sleep apneas. Brodeur, et al., "Treatment of restless legs syndrome and periodic movements during sleep with L-dopa: A double-blind, controlled study", Neurology, 38, 1845 (December 1988). Bedtime is a major problem for these patients since rest, particularly lying down in bed, is associated with increased dysesthesia and irresistible leg movements, which interfere with sleep onset. Most frequently, the patients move their legs vigorously, flexing, stretching, and crossing them one over the other. The intensity of muscular jerks can vary greatly from one case to another. Often, patients have to get out of bed several times a night.
Nearly all patients with RLS also experience stereotyped, repetitive movements once asleep, a condition known as periodic movements during sleep or periodic limb movement syndrome (PLMS). Periodic movements during sleep represent a distinct nosological entity from RLS. Independent PLMS occurs along with a wide range of sleep-wake complaints, including early sleep onset difficulty, nocturnal awakenings, and daytime sleepiness. See Kryger, et al., "Principles and Practice of Sleep Medicine", 1989, Saunders Company, Chapter 43; Culpepper, et al., "Time of Night Patterns in PLMS Activity", Sleep, 15(4):306-311; .Shahal, et al., "Cyclic Leg EMG Activity During NREM-REM Sleep in Patients with Period Leg Movements in Sleep", Sleep Research???; Valencia, et al., "Incidence of Sleep Apnea and Nocturnal Myoclonus Among Elderly Females in a Mexican Population", Sleep Research, 1990, 19:303; Becker, et al., "Reliability of Bedpartner's Reports for Symptoms of Sleep Apnea and Periodic Leg Movements", Sleep Research, 1990:19:188; Sandyk, et al., "Serotonin in Involuntary Movement Disorders", Int. J. Neuroscience, 1988; 42-43; Kotagal, et al., "Relationship of EEG Changes to Periodic Leg Movements", Sleep Research, 1990; 19:244; Shafor, et al., "Lumbo-Sacral Spine Abnormalities and Periodic Leg Movements in Sleep", Sleep Research, 1990:19:292; Shahal, et al., "Cyclic Leg EMG Activity During NREM-REM Sleep", Sleep Research, 1990:19:130
Treatment of RLS and PLMS has varied and includes clonazepam and other benzodiazepines, propoxyphene and other opiates, and L-dopa and other dopoaminergic drugs, for example. See Montplaisir, et al., "The Treatment of Restless Leg Syndrome With or without Periodic Leg Movements in Sleep", Sleep, 15(5):391-395 (1992) and Kryger, et al., supra; Bonnet, et al., "The Use of Triazolam in Older Patients With Periodic Leg Movements, Fragmented Sleep, and Daytime Sleepiness", Journal of Gerontology: Medical Sciences, 1990, Vol. 45, No. 4, M139-144; Scrima, et al., "Gamma-Hydroxybutyrate Effect on Nocturnal Myoclonus: A Double-Blind Study", Sleep Research, 1990; 19:289; Bamford, et al., "Letter Failure of Clonidine to Ameliorate the Symptoms of Restless Legs Syndrome", Sleep, 10(4):398-399 (1987); Guilleminault, et al., "Periodic leg movement, sleep fragmentation and central sleep apnea in two cases: reduction with Clonazepam", Dur. Respir. J., 1988, 1, 762-765. Further on the use of L-dopa can be found in the following publications: Brodeur, et al., supra; Guilleminault, et al., "Periodic Leg Movement, L-Dopa, 5-Hydroxytryptophan, and L-Tryptophan", Sleep, 10(4):393-397 (1987).
While L-dopa has been used somewhat successfully in the treatment of PLMS, often-repeated dosages over the course of the night are required. Dosages effective in the treatment of PLMS also can lead to daytime drowsiness in some patients. The sustained-release form of carbidopa-levodopa was thought to be the answer to repeated nighttime dosages; however, this has not been borne out in clinical studies. Thus, a new regimen is needed in order to deal effectively with patients afflicted with PLMS.